Microglia-Derived Microvesicles Affect Microglia Phenotype in Glioma

小胶质细胞衍生的微囊泡影响胶质瘤中的小胶质细胞表型

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作者:Alfonso Grimaldi, Carmela Serpe, Giuseppina Chece, Valentina Nigro, Angelo Sarra, Barbara Ruzicka, Michela Relucenti, Giuseppe Familiari, Giancarlo Ruocco, Giuseppe Rubens Pascucci, Francesca Guerrieri, Cristina Limatola, Myriam Catalano

Abstract

Extracellular-released vesicles (EVs), such as microvesicles (MV) and exosomes (Exo) provide a new type of inter-cellular communication, directly transferring a ready to use box of information, consisting of proteins, lipids and nucleic acids. In the nervous system, EVs participate to neuron-glial cross-talk, a bidirectional communication important to preserve brain homeostasis and, when dysfunctional, involved in several CNS diseases. We investigated whether microglia-derived EVs could be used to transfer a protective phenotype to dysfunctional microglia in the context of a brain tumor. When MV, isolated from microglia stimulated with LPS/IFNγ were brain injected in glioma-bearing mice, we observed a phenotype switch of tumor associated myeloid cells (TAMs) and a reduction of tumor size. Our findings indicate that the MV cargo, which contains upregulated transcripts for several inflammation-related genes, can transfer information in the brain of glioma bearing mice modifying microglial gene expression, reducing neuronal death and glioma invasion, thus promoting the recovery of brain homeostasis.

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